Complicated Grief in Older Adults: Physiological Substrates of Emotion Regulation This application for a Career Development Award in Aging describes an integrated training plan and research project to allow the candidate to become an expert in the physiological underpinnings of emotion regulation in older adults. Conjugal bereavement is highly prevalent in older adults, with more than 900,000 people widowed each year in the U.S. Although most adjust gradually to widow(er)hood, others experience a complicated course. Complicated grief, which persists despite anti-depressant treatment, has been found to be an independent predictor of cognitive decline, poor health, depression and suicidality in older adults, making it a major public health concern. Cognitive factors, such as the inability to shift attention away from intrusive thoughts of the deceased are hypothesized to impair adjusting to a life as a widow(er). Furthermore, physiological mechanisms, such as low-grade inflammatory processes, may contribute to emotional dysregulation found in this population. The proposed research will assess neural activation, immune markers, and neuropsychological tests of attention and emotion regulation in older adults. We will recruit 135 older adults (45 with complicated grief, 45 with uncomplicated grief and 45 non-bereaved, determined by a structured interview with new consensus criteria). The specific aims are: Aim 1) To examine attentional deficits in older adults with complicated grief as measured by the e-Stroop as compared to controls (uncomplicated grief and non-bereaved); Aim 2) To examine the neural substrates of attentional deficits in a subsample of 36 older adults with fMRI in these three groups; Aim 3) To evaluate circulating markers of inflammation (e.g., sTNF-RII, IL-6, slL-6R and IL-1Ra) in older adults with complicated grief as compared to controls (uncomplicated grief and non-bereaved). The long-term goal of the project is to explore whether neural activity mediates the relationship between circulating markers of inflammation and attentional deficits. The Cousins Center for Psychoneuroimmunology at UCLA has both excellent resources (e.g. 3T imaging scanner) and excellent mentors (including Dr. Michael Irwin, MD) necessary for advanced training in bereavement, immunology, and neuroimaging research that will facilitate development of the candidate, Dr. Mary-Frances O'Connor, into an independent investigator and allow her to develop an R01 proposal to evaluate treatment for complicated grief, based on both physiological and psychological mechanisms. [unreadable] [unreadable] [unreadable]